Rossiello Luigi, D'Andrea Francesco, Grella Roberto, Signoriello Giuseppe, Abbondanza Ciro, De Rosa Caterina, Prudente Mariaevelina, Morlando Marianna, Rossiello Raffaele
Department of Human Pathology, Division of Clinical Pathology, II University of Naples, via L. Armanni 20, Naples, Italy.
Wound Repair Regen. 2009 Sep-Oct;17(5):750-7. doi: 10.1111/j.1524-475X.2009.00530.x.
Hypertrophic scar (HS) and keloid (KL) are two forms of an abnormal cutaneous scarring process, mainly characterized by excessive extracellular matrix deposition and fibroblast proliferation. Despite the increased understanding of the molecular and cellular events leading to HS and KL, the pathogenesis of these lesions remains poorly understood. A pivotal role in the formation of abnormal scars has been ascribed to transforming growth factor-beta, whose activity appears to be mediated through a link with pathways acting via cyclooxygenases (COX-1 and COX-2). To date, there is no report on the in vivo expression of COX-1 and COX-2 in human HS and KL tissues. Therefore, using immunohistochemistry and Western blot analysis, we investigated 36 cases of KL, 32 cases of HS, and 25 cases of normal skin in order to define the localization and distribution of COX-1 and COX-2 in the tissues of these scar lesions and the overlying epidermis. The results mainly show the following: (a) a significant overexpression of COX-1 in HS tissues and the overlying epidermis as compared with normal skin and KL tissues and (b) a significant overexpression of COX-2 in KL tissue and the overlying epidermis in contrast to normal skin and HS tissues. Our data support the hypothesis that both COXs are involved in the pathogenesis of scar lesions in different ways and, particularly, COX-1 in the formation of HS and COX-2 in the formation of KL. In addition, the overexpression of COX-1 and COX-2 in the epidermis overlying HS and KL tissues, respectively, underlines the importance of epithelial-mesenchymal interactions in the pathogenesis of scar lesions.
肥厚性瘢痕（HS）和瘢痕疙瘩（KL）是异常皮肤瘢痕形成过程的两种形式，主要特征是细胞外基质过度沉积和成纤维细胞增殖。尽管对导致HS和KL的分子和细胞事件的了解有所增加，但这些病变的发病机制仍知之甚少。转化生长因子-β在异常瘢痕形成中起关键作用，其活性似乎通过与环氧化酶（COX-1和COX-2）作用的途径相关联来介导。迄今为止，尚无关于COX-1和COX-2在人HS和KL组织中体内表达的报道。因此，我们采用免疫组织化学和蛋白质印迹分析，研究了36例KL、32例HS和25例正常皮肤，以确定COX-1和COX-2在这些瘢痕病变组织及上方表皮中的定位和分布。结果主要显示如下：（a）与正常皮肤和KL组织相比，HS组织及上方表皮中COX-1显著过表达；（b）与正常皮肤和HS组织相比，KL组织及上方表皮中COX-2显著过表达。我们的数据支持以下假设，即两种环氧化酶均以不同方式参与瘢痕病变的发病机制，特别是COX-1参与HS的形成，COX-2参与KL的形成。此外，COX-1和COX-2分别在HS和KL组织上方的表皮中过表达，突显了上皮-间质相互作用在瘢痕病变发病机制中的重要性。
